It's challenging to get people to volunteer for dementia clinical trials, especially with mild symptoms

Portland, Oregon (CNN) -- There was cake at one of the last birthdays Robert John Kreitner Jr. would have at the nursing home in Pennsylvania, but the guest of honor didn't open his eyes to see it.

His wife propped him up at the end of the table. Their son Phil couldn't help thinking the scene macabre.

Phil Kreitner's father, a self-taught engineer, was firm-minded and hated to concede a point. Only once in the last 12 years of his life had Robert Kreitner admitted he had trouble remembering things. Now that his son is having memory problems of his own, he vows he'll never end up in a nursing home like his father, but won't deny what's happening to his brain.

"It's helpful to me that my father had Alzheimer's, because it makes it much easier for me to accept the existence of it, the reality of it, and the personalization of it, and the finality of it," says Kreitner, 71, of Portland, Oregon.

Kreitner has mild cognitive impairment, an early stage of dementia that researchers consider a prime window of opportunity to try potential treatments to stop the progression of memory loss and cognitive decline. A person with mild cognitive impairment has a measurable memory problem, but no language or general thinking difficulties and is still able to function, says Dr. Joseph Quinn, researcher at Oregon Health & Sciences University and Portland VA Medical Center.

Not everyone who has mild cognitive impairment will worsen and develop Alzheimer's disease, but there are certain signatures in the brain -- plaques formed from a protein called beta-amyloid -- that indicate a high likelihood of Alzheimer's in patients who are already having memory problems. The plaques can be identified through MRI and PET scans.

"My memory is a jigsaw puzzle and it's just been dumped out of the box," Kreitner says. "If I were to have to reconstruct that puzzle, I couldn't do it."

Kreitner believes it's his duty to humankind join the effort to fight Alzheimer's, the disease that ultimately took his father's life. The condition affects about 5.4 million people in the United States and is projected to affect 16 million by 2050.

That's why Kreitner is participating in a clinical trial that is investigating a drug in patients with mild cognitive impairment.

"My father was very militaristic, so I've had this stuff beat into my head my whole life: You have a responsibility to the collectivity, however the collectivity is defined. No man is an island," Kreitner says.

Getting patients into trials

Alzheimer's researchers wish they found more people with Kreitner's attitude, but in practice it's hard to get patients into clinical trials for Alzheimer's and dementia.

One problem is that some people want to join a trial only if they know for certain they will be trying an experimental drug. But scientifically valid medical studies are "double-blind," meaning neither the researchers nor the participants know who's getting real medicine or and who's getting a fake treatment called a placebo.

That is the strongest way to demonstrate that taking a drug works better than doing nothing. It also means that some participants will go through the entire trial process without trying the experimental treatment. Even some physicians try to get their patients in the drug treatment groups, but it goes against the standard method of trials for the experimenters to know who is getting what treatment, says William Thies, chief medical and scientific officer at the Alzheimer's Association.

There are also practical issues with elderly patients' participation, such as transportation and coordinating with caregivers. In the early stages of dementia, patients are still able to make decisions about joining trials. For later-stage patients, the caregiver has the burden of finding a study and taking the patient through the process.

It is especially challenging to recruit for mild cognitive impairment trials because people are more reluctant to come forward with mild problems, Quinn says. Also, some people don't want to take on the potential risks of an experimental drug.

The Alzheimer's Association's TrialMatch website, which launched last year, aims to help people find appropriate trials that are convenient to them. The website lists more than 120 trials. So far, almost 12,000 people have completed profiles on the website; the Alzheimer's Association is in the process of helping them find appropriate trials.

"Without trial volunteers, we actually won't have the next new medication. If everybody actually understood how critical their participation might be in making a better future, probably we'd have many more people volunteering for trials," Thies says.

An experimental drug

Kreitner is taking part in a phase II drug trial sponsored by Bristol-Myers Squibb. Quinn is the principal investigator for the portion of the trial at Oregon Health & Sciences University, one of dozens of sites across the country.

The drug in question is a gamma secretase inhibitor, a class of drug that is supposed to interfere with the formation of plaques of beta-amyloid proteins in the brain.

The news around gamma secretase inhibitors hasn't been good so far -- at least in patients with Alzheimer's. Last year, Eli Lilly announced it would halt the development of semagacestat, a gamma secretase inhibitor, because two ongoing long-term phase III studies indicated that it didn't slow the progression of Alzheimer's; researchers found an association with worsening of cognitive symptoms, too.

But Quinn and colleagues are hoping that a drug of the same type will work in patients with mild cognitive impairment, given that their brains have not built up as much pathology.

Documented risks of this drug include increased incidence of relatively benign skin cancer, gastrointestinal problems and brain swelling, he says.

So far, Kreitner says he has felt no side effects. Every two or three months, he gets brain scans and spinal taps so researchers can check for the biomarkers associated with dementia. He doesn't mind the process, not even when they stick a needle into his spinal column.

"It's my personal feeling that I'm making literally no sacrifice except to force myself to remember to take these capsules every day," he says.

Life in the shadow of Alzheimer's

Kreitner has had myriad careers: naval officer, adjunct professor, massage therapist, environmentalist and demographer, among other things. He's also a master at the rowing machine and logs 90 minutes a week. He snagged second place at the World Indoor Rowing Championship in Boston in his age group this year.

You can tell he has done a lot of thinking about society's failings, and admits he has always felt a general dissatisfaction with the world and himself. He's always been someone who self-assesses, striving to stay in good shape; these days, that includes monitoring his own mental functioning.

His wife, Sherril Gelmon, professor of public health at Portland State University, noticed Kreitner's forgetfulness about two years ago. Kreitner himself became aware of small lapses; he would find himself in a room and forget his purpose for being there, for example. The two began to get edgier with each other, which is uncommon in their 13 years of marriage.

She went with Kreitner to the Layton Aging and Alzheimer's Disease Center at Oregon Health & Sciences University. The couple wanted to know if Kreitner would be eligible for any treatments, and learned about the Bristol-Myers Squibb trial. Quinn told them Kreitner could be eligible, and after an official screening, Kreitner joined the study.

After Gelmon recounts this history, Kreitner smiles and says that he wouldn't have been able to give all those details himself.

"I'm at the stage where everything that Sherril just said rings a bell," he says. "If you were to ask me, 'What's happened in the past couple of years relating to this?' I couldn't have given you 10% of that."

Members of both sides of Gelmon's family have had dementia. Her father died in 2009 and her mother is in the advanced stages, so she's also familiar with the realities of the condition. She monitors her own mental state, but doesn't wake up afraid of it. She and Kreitner talk regularly about how they might need to adjust their lifestyle, if at all, if Phil's condition were to worsen.

"It's hard when you're not as good at what you're doing as you used to be. I wouldn't say we're depressed; I would say frustrated, upset. Since both of us have watched parents go through it, we've already done a certain level of coping," Gelmon says.

Toward the end

Before his death, Kreitner's current goal is to write a book -- and if he can't get there, a 1,500-word article -- about how he views the world. He says it's an "an adjuration to my fellow humans to start thinking like a species; my hypothesis is that we're on an individual, class, ethnic, national, racial self-destruction trip, and we're taking the planet down in the struggle."

Remembering how his mother suffered trying to take care of his father at home, and visiting him in the nursing home, Kreitner doesn't want to burden Gelmon in the same way, nor does he see himself in a nursing home.

But if he gets to a point that he deems too far along, he's resolved, even though it is not legal, to find a way to "check out" of life.

"I will give proper notice. It will not be specific but it will be implicit that I feel that the time is now or never. I will bear complete responsibility for any actions that result in my death. I will not make a mess," he says.

Gelmon shows no anguish when her husband speaks this way; she is calm and matter-of-fact when she says: "My expectation is that if and when we get to that point, we will have discussed it at length and it will not be a surprise. It will still make me very sad, but if we're communicating well and early, then it should not come as a surprise and it should be something I'm as informed about as he's willing to inform me."

In the meantime, Kreitner continues to follow the regimen of gray capsules prescribed by the clinical trial. He relies on notes, a lot of them, to remember to keep appointments, and often waits for memories to make their way up through the mud in his mind.

"We've got way more human beings on this planet than it could sustain, even if we were sane. Who the hell am I? When my effectiveness is gone, I'm gone," he says. "Lead, follow, or get out of the way."